In experimental models, endothelial injury is an important intiating event for atherosclerosis, thrombosis, and immune vasculitis. We propose to examine the role of viruses and immunologic events as inducors of vessel wall injury. In preliminary studies we demonstrated that several common human viruses replicate within endothelial and smooth muscle cells in vitro. We examined one virus, herpes simplex (HSV), in detail and showed: 1) that HSV I infection of human umbilical vein cells activates complement on the cell's surface in the absence of antiviral antibody; 2) that HSV induces receptors for the Fc portion of IgG and for C3b on the cell's surfacr; and 3) that HSV can initiate a persistent infection of endothelial cells. We also noted that sera from patients with active systemic lupus erythematosis and thrombotic thrombocytopenic purpura demonstrated increased binding of IgG to uninfected endothelial cells. In this proposal we will further characterize the susceptability of smooth muscle cells to common human viruses using immunfluorescence, cytopathology, and growth curve assays. We will comparer viral growth in endothelial cells of arterial and venous origin. We will characterize the HSV persistent infection by performing quantitative viral assays, and will monitor endothelial cell functions during persistent infection. We will attempt to establish models of persistent infection of smooth muscle cells. We will characterize the pathway, mechanisms and kinetics of antibody-independent activation of complement following viral infection of endothelium. We will study in detail the HSV-induced C3b receptor and determine whether this receptor is a structural component of the virus. We will determine if sera from patients with vasculitic disorders have anti-endothelial cell activity and quantitate immunoglobulin and complement binding by RIA. Finally we will monitor the effects that acute and persistent viral infection, complement activation and immune complex binding have on the function of vessel wall cells by monitoring cell morphology, viability, adherence of granulocytes and platelets and elaboration of prostacyclin.